Stem cell membrane-cloaked biomimetic nanoparticles targeted delivery of Naringin to control cytokine storm in mouse pneumonia

Background: Cytokine storm or cytokine release syndrome (CRS), mainly caused by the bacteria, viruses, etc., is life-threatening systemic inflammatory syndrome. CRS in the lung can lead to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in a very short time, and it is the main reason for patients with mild symptoms transferring to severe disease even death. Thus, effectively controlling CRS is essential in the prevention and treatment of infectious pneumonia. Methods: The naringin nanoparticles (Nar-NPs) were prepared by emulsification-and-evaporation method, and then the mesenchymal stem cell membranes were extracted and coated onto the surface of Nar-NPs by hand extrusion through nano-porous membranes to obtain cell membrane (CM) cloaked CM@Nar-NPs. The biocompatibility, inflammation-targeting, antioxidant capacity and anti-inflammatory efficiency were determined both in vitro and in vivo . Results The as-synthesized biomimetic platform (CM@Nar-NPs) showed highly efficient targeting and Nar delivery to the macrophages and alveolar epithelial cells as demonstrated by fluorescent imaging and flow cytometry analyses. The lung inflammation-targeting and accumulation of CM@Nar-NPs were also confirmed by IVIS imaging in septic mice. In LPS-induced sepsis mouse model, CM@Nar-NPs showed efficient therapeutic efficacy, as evidenced by improved survival rate, decreased pulmonary permeability and cytokine release, and the organ damage protection. Additionally, CM@Nar-NPs exhibited excellent antioxidant capacity, as evidenced by ROS scavenging in inflamed RAW264.7 cells and in the lung and liver of septic mice. To further determine the protective mechanism of CM@Nar-NPs, infiltrated macrophages in the lung were isolated and analyzed. CM@Nar-NPs increased the expression of M2 marker (CD206), and decreased the expression of M1 marker (F4/80) in septic mice, suggesting that Nar-modulated macrophages polarizing towards M2 subtype might contribute to their anti-inflammation effects. Conclusion The as-synthesized biomimetic platform (CM@Nar-NPs) can be employed to targeted delivery and improve the therapeutic efficacy of active ingredients from herbal medicine in the treatment of inflammatory diseases. This nanoplatform shows potential prospects for pneumonia-targeted delivery in clinics.